Small RNA sequencing reveals microRNAs related to neuropathic pain in rats

Abstract

The present study aimed to identify microRNAs (miRNAs) that are involved in neuropathic pain and predict their corresponding roles in the pathogenesis and development process of neuropathic pain. The rat model of neuropathic pain caused by spared nerve injury (SNI) was established in Sprague-Dawley male rats, followed by small RNA sequencing of the L3–L6 dorsal root ganglion. Real-time PCR was performed to validate the differently expressed miRNAs. Functional verification was performed by intrathecally injecting the animals with miRNA agomir. A total of 72 differentially expressed miRNAs were identified in the SNI rats, including 33 upregulated and 39 downregulated miRNAs. The results of qPCR further verified the expression levels of rno-miR-6215 (P=0.015), rno-miR-1224 (P=0.030), rno-miR-1249 (P=0.038), and rno-miR-488-3p (P=0.048), which were all significantly downregulated in the SNI rats compared to the control ones. The majority of differentially expressed miRNAs were associated with phosphorylation, intracellular signal transduction, and cell death. Target prediction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses suggested that these differentially expressed miRNAs targeted genes that are related to axon guidance, focal adhesion, and Ras and Wnt signaling pathways. Moreover, miR-1224 agomir significantly alleviated SNI-induced neuropathic pain. The current findings provide new insights into the role of miRNAs in the pathogenesis of neuropathic pain.

Analgesic effect of dexmedetomidine in rats after chronic constriction injury by mediating microRNA‐101 expression and the E2F2–TLR4–NF‐κB axis

“…Recently, microRNAs (miRNAs) have been revealed to play vital roles in modulating pain transmission in animal experiments and clinical studies (Dai et al., 2019). For instance, hsa‐miR‐101‐3p has been identified as one of the seven miRNAs that were reduced after delivery of Dex to the subjects (Yang et al., 2018).…”

The etiological roles of miRNAs, lncRNAs, and circRNAs in neuropathic pain: A narrative review

“…One week after spared nerve injury (SNI), 33 and 39 miRNAs in the DRG were upregulated and downregulated, respectively, with most DE miRNAs related to axon guidance, focal adhesion, Ras and Wnt signaling pathways. 18 Furthermore, nerve injury‐induced miRNAs expression was dynamic and time‐dependent, 19 , 20 implicating multiple regulatory mechanisms in neuropathic pain initiation and development. Nerve injury redistributes miRNAs from a uniform style within the DRG soma of non‐allodynic animals to preferential localization to peripheral neurons in allodynic animals.…”

DNA Methylation and Non-Coding RNAs during Tissue-Injury Associated Pain

“…This varies from standard RNA-Seq in employing electrophoresis-based fractionation to specifically separate small RNA, followed by universal adapter ligation on both ends of the RNA fragment and posterior amplification. Using small RNA-Seq, Dai’s group has identified 33 upregulated and 39 downregulated miRNAs used at L3-L6 DRG of rats that were subjected to the SNI model [ 60 ]. Moreover, Zhou and colleagues discovered 134 lncRNA, 12 miRNA and 188 circRNA in the rats’ spinal cord following spinal nerve injury [ 58 ].…”